36.13). An elevated ionized plasma [Ca • Fig. 36.14 Overview of Ca++ homeostasis. PTH, parathyroid hormone. (From Koeppen BM, Stanton BA. Renal Physiology. 5th ed. Philadelphia: Elsevier; 2013.) arrhythmias, lethargy, disorientation, and even death.
This effect of hypercalcemia occurs because an elevated plasma [Ca++] causes the threshold potential to shift to less negative values (i.e., farther from the resting membrane voltage). Plasma [Ca++] is regulated within a very narrow range, primarily by parathyroid hormone (PTH), calcitriol (1,25-dihydroxyvitamin D), the active metabolite of vitamin D3, and plasma Ca++ , and this regulation will be discussed next.
Within cells, Ca++ is sequestered in the endoplasmic reticulum and mitochondria, or it is bound to proteins. Thus the free intracellular [Ca++] is very low (≈100 nM). The large concentration gradient for [Ca++] across cell membranes is maintained by a Ca++-ATPase pump (PMCa1b) in all cells and by a 3Na+/Ca++ exchanger (NCX1) in some cells.
Overview of Calcium Homeostasis
Ca++ homeostasis depends on two factors: (1) the total amount of Ca++ in the body and (2) the distribution of Ca++ between bone and ECF. The total body Ca++ level is determined by the relative amounts of Ca++ absorbed by the intestinal tract and excreted by the kidneys (Fig.
36.14 ). The intestinal tract absorbs Ca++ through an active carrier-mediated transport mechanism that is stimulated by calcitriol, the active metabolite of vitamin D3 that is produced in the proximal tubule of the kidneys. Net Ca++ absorption by the intestine is normally 200 mg/day, but it can increase to 600 mg/day when calcitriol levels rise. In adults, Ca++ excretion by the kidneys equals the amount absorbed by the GI tract (200 mg/day), and it changes in bIn clinical practice the terms hypercalcemia and hypocalcemia are often used to describe a high or low total plasma [Ca++], respectively, even though this usage is not the physiologically correct usage of hypercalcemia and hypocalcemia.
parallel with intestinal absorption. Thus in adults, Ca++ balance is maintained because the amount of Ca++ ingested in an average diet (1000 mg/day) equals the amount lost in feces (800 mg/day, the amount that escapes absorption by the intestinal tract) plus the amount excreted in urine (200 mg/day).
The second factor that controls Ca++ homeostasis is the distribution of Ca++ between bone and ECF (see